Emerging trends and hotspots in peptic ulcer from 2008 to 2023: A bibliometric analysis

Peptic ulcer (PU) is a common digestive disorder in the gastroduodenal. Although bibliometrics has become very popular in the medical field, a bibliometric analysis of research related to PU has yet to be reported. Therefore, this research aims to analyze the trends and hotspots of PU in the last 15 years. Literature data related to PU retrieved from the Web of Science Core Collection database from 2008 to 2023 were visualized and analyzed using CiteSpace 6.1.6.msi, VOSviewer 1.6.19, and SCImago Graphica Beta 1.0.35. Six thousand four hundred ninety-one papers were collected based on inclusion and exclusion criteria. The country with the highest number of publications was China. The institution with the highest number of publications was Baylor College of Medicine. The most prolific author was Yamaoka Yoshio. Malfertheiner Peter had the highest number of citations. The journal with the most publications is World Journal of Gastroenterology. The most cited Journal is Gastroenterology. The most cited reference was published by Marshall B. J. et al in 1984. The article with the highest burst strength was published in 2012 by Malfertheiner Peter. The keyword with the highest burst strength was “oxidative stress.” Our research provides a bibliometric analysis of PU research to reveal the trends and hotspots of PU for 2008 to 2023. Our findings will help researchers to quickly understand the current state of research and provide a reference for in-depth studies in this area to foster the development of PU research.


Introduction
Peptic ulcer (PU) is a break of >3 to 5 mm in the mucosa of the stomach or duodenum with a visible depth. [1]The clinical manifestations of PU are epigastric pain, nausea, early satiety, bloating, belching, or postprandial discomfort. [1,2]Complications include bleeding, perforation, penetration, and gastric outlet obstruction, [3] with Helicobacter pylori (H pylori) and nonsteroidal anti-inflammatory drugs (NSAIDs) as significant risk factors. [4,5]PU affects 4 million people worldwide each year, with an estimated lifetime prevalence of 5% to 10% in the general population. [6]bliometrics can analyze the literature in a particular field to understand its knowledge structure and explore its development trend.It can be combined with CiteSpace, VOSviewer, and other visual analysis software to show the current research status and hotspots of a specific field in the form of images, which explore the relationship between countries, institutions, authors, journals, cited literature, and keywords. [7]It has been applied to the research of cancer, [8] cardiovascular system diseases, [9] and endocrine system diseases. [10]However, there is no bibliometric analysis study on PU.Therefore, this study systematically analyzes the studies on PU between 2008 and 2023 and evaluate the current status and trends of related research.

Materials and methods
We searched the Web of Science Core Collection for Science Citation Index Expanded (SCI-Expanded) and downloaded the data on June 23, 2023.Search terms included: TS = (Gastroduodenal Ulcer OR Peptic Ulcer).Limit publication time to from January 1, 2008 to May 13, 2023, and the document type was restricted to thesis and review papers, excluding non-English literature.We ended up with 6491 articles and reviews that met the inclusion criteria for analysis.

Annual numbers of publications
As shown in Figure 1, 7970 papers related to PU were published between January 01, 2008 and May 13, 2023.According to the inclusion and exclusion criteria, a total of 6491 papers were obtained, which were written by 30,240 authors from 6644 institutions in 132 countries, published in 1554 journals, and cited 155,158 times by 19,443 journals.
As shown in Figure 2, the number of papers published from 2008 to 2022 remained steady at more than 370.The lowest in 2018 (n = 373) and peaked in 2014 (n = 470), indicating that PU has always been on the minds of scholars.

Analysis of countries
The study utilizes VOSviewer and Scimago Graphica for country visualization and analysis.Among the top 10 countries ranked in terms of the number of publications, China has the highest number of publications (1252 publications) but a low average number of citations, followed by the United States (1235 publications) and Japan (620 publications).In addition, the United Kingdom, Germany, and Italy had the highest average citations, indicating a high level of scientific research in European countries (Fig. 3A and B; Table 1).The country with the highest number of collaborations with other countries is the United States, followed by the United Kingdom and China.The lines in the graph indicate collaboration, and the darker the color, the more collaboration with other countries, the way most countries have light colors, indicating that these countries do not have stable communication and collaboration (Fig. 3C  and D).

Analysis of institutions
VOSviewer was used to map the visualization of the institutions.The top 10 institutions in terms of publications are shown in Table 2, with Baylor Coll Med (108 publications) having the highest number of publications, followed by Chinese Univ Hong Kong (97 publications) and China Med Univ (95 publications).7/10 of the institutions in Asia.However, the United States institutions (Baylor Coll Med and Michael E DeBakey VA Med Ctr) have the highest average citations, with the top 100 most published institutions centered on Baylor Coll Med (Fig. 4).

Analysis of authors and cited authors
The top 10 authors in terms of publications ranked Yamaoka Yoshio (68 publications) first, followed by Lanas Angel (42 publications) and Graham David Y. (35 publications).Malfertheiner Peter (126.90 average citations) had the highest average number of citations, followed by Graham David Y. (119.06 average citations) and Chan Francis K. L. (117.21 average citations) (Fig. 5A; Table 3).Among the top 10 co-cited authors ranked in terms of paper citations, Malfertheiner Peter has the most citations, with 5 out of 30,240 co-cited authors having been cited more than 1000 times, which suggests that their scholarship is recognized and cited by the majority of scholars (Fig. 5B; Table 4).

Analysis of journals and cited journals
Table 5 lists the top 10 journals ranked in terms of the number of papers published related to PU, with an average impact factor of 4.46.These journals accept the most significant number of articles related to PU and are recommended to be followed by scholars researching PU.World Journal of Gastroenterology (223 publications) is the most prolific journal in this field, followed by Helicobacter (157 publications) and Plos One (121 publications) (Fig. 6A; Table 5).Impact factor (IF) is an internationally recognized journal evaluation metric.Among the top 10 journals selected, Alimentary Pharmacology & Therapeutics (IF = 9.524) has the highest impact factor and average citation frequency.Table 6 shows the top 10 cited journals related to PU.Most of these magazines are Q1 in the Journal Citation Reports.The most cited journal was Gastroenterology (10,831 citations), followed by American Journal of Gastroenterology (9219 citations) and Gut (8402 citations) (Fig. 6B; Table 6).The higher average impact factor (IF = 49.05) was due to the high impact factors of Lancet (IF = 202.731)and New England Journal of Medicine (IF = 176.082).World Journal of Gastroenterology, Helicobacter, Alimentary Pharmacology & Therapeutics, and Digestive Diseases and Sciences are present in Tables 5 and 6, indicating that these journals have received wide attention in gastroenterology.

Analysis of references
Citespace and VOSviewer were used to map the visualization of the references.The top 10 references cited in PU research were all published between 1984 and 2012.The most cited reference is "Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration." by Marshall, B. J. et al 1984, which was cited 301 times (Fig. 7A; Table 7).Based on the burst detection analysis of the references, the results of the first 25 articles are shown in Figure 7B.Burst detection identifies articles that are intriguing to people in a specific period.The article with the highest burst strength was published in 2012 by Malfertheiner Peter in Gut: Management of Helicobacter pylori infection-the Maastricht IV/ Florence Consensus Report.

General information
We screened a total of 6491 papers on PU from Web of Science Core Collection, and the number of papers has steadily increased during this period of 15 years.China has the most significant number of papers published and has made outstanding contributions to PU research.In addition, 4 of the top 10 research institutions are from China, including Chinese Univ Hong Kong, China Med Univ, Natl Yang Ming Univ, and Chang Gung Univ, which indicates that Chinese institutions have paid   In addition, the United States has carried out extensive cooperation in this field, which is much higher than other countries, so other countries should pay more attention to interregional cooperation and exchange.Yamaoka Yoshio is the author with the most publications in this field and is primarily involved in the pathogenesis of gastroduodenal diseases associated with H pylori. [11,13,17,18] Malfertheiner Peter is the author of the most cited papers in this field and is primarily involved in developing the management of H pylori infections, one of the causes of PU. [15,16,19] World Journal of Gastroenterology is the most included journal, with an IF of 5.374.The journal is published in the United States and focuses on articles in gastroenterology and hepatology.Gastroenterology is the most cited journal, with an IF of 33.883.The journal is  Lanas, Angel [12] 1157 6 Yamaoka, Yoshio [11]     10 papers with the most cited papers, suggesting that H pylori continues to be a hot research topic in recent years.

Hotspots and frontiers
Combining the frequency of keywords, timeline mapping, and burst word mapping, we summarized the research hotspots and development directions in the field of PU.

Pathogenic mechanisms and risk factors of PU.
H pylori and the use of NSAIDs are major risk factors for PU. [20] pylori is a gram-negative, spiral-shaped, microaerobic bacterium that colonizes the human gastric mucosa.H pylori infection is closely associated with PU, and bacterial and host factors mediate its pathogenesis.H pylori utilizes urease to neutralize the stomach's acidic environment [21,22] and flagella to regulate motility towards the gastric epithelium [23] and successfully colonize and establish a persistent infection.It secretes outer membrane proteins, including blood group antigen-binding adherence and sialic acid-binding adherence, which interact with antigens in the gastroduodenal tract to promote bacterial adhesion to the gastric epithelium, [24] and finally release a variety of virulence factors, including cytotoxin-associated gene A and vacuolating cytotoxin A, leading to gastric tissue damage. [25,26]H pylori induces chronic inflammation in the gastric mucosa mediated by a range of pro-and anti-inflammatory cytokines, and host gene polymorphisms can cause PU by influencing inter-individual differences in the degree of cytokine response, leading to an imbalance between attack and defense factors in the mucosa.Several pro-inflammatory cytokines (IL-1B, IL-6, IL-8, and TNF-α) and anti-inflammatory cytokines (IL-10) are associated with PU. [27] NSAIDs are commonly used to treat inflammatory pain.The mechanisms by which NSAIDs produce damage to the gastroduodenal can be categorized into local and systemic actions, including the induction of injury by 3 key pathways: inhibition of cyclooxygenase-1 activity, inhibition of cyclooxygenase-2 activity, and direct cytotoxicity effects on the epithelium. [28]ystemic inhibition of cyclooxygenase-1-derived prostaglandins is thought to be the primary mechanism.Reduced mucosal prostaglandin levels are associated with decreased mucus and bicarbonate secretion, inhibition of cell proliferation, and decreased mucosal blood flow, which is essential for maintaining mucosal integrity, therefore reduced mucosal prostaglandin levels lead to PU. [12] 4.2.2.Diagnosis of PU.PU clinically manifests itself in epigastric pain, dyspepsia, and other symptoms, and endoscopy is the gold standard for diagnosing PU.Since H pylori is a significant cause of PU, examination of H pylori is essential.Diagnostic methods for H pylori infection can be categorized as invasive and noninvasive.Invasive testing involves a biopsy sample obtained during esophagogastroduodenoscopy, which is then subjected to histologic analysis, rapid urease assay, molecular methods, or culture to diagnose the presence of H pylori infection.Noninvasive tests include serologic testing, fecal antigen testing, 13C-urea breath testing, and so on. [29]he American Society for Gastrointestinal Endoscopy recommends esophagogastroduodenoscopy for patients over 50 years of age suspected of having PU, and noninvasive testing for H pylori such as the 13C-urea breath testing and fecal antigen testing for patients under 50 years of age with no symptoms other than dyspepsia. [30,31]2.3.Treatment of PU.The eradication of H pylori is crucial as it is one of the main factors causing PU.Therapeutic regimens for H pylori eradication are based on a combination of strong acid inhibitors and antibiotics.The main clinical programs are proton pump inhibitor triple (PPI) therapy, bismuth quadruple therapy, and the resulting sequential, concomitant, and hybrid therapies.
PPI triple therapy (PPIs plus 2 antibiotics: clarithromycin, amoxicillin, or metronidazole) for 7 to 10 days used to be the standard of care and was the first-line treatment option for H pylori eradication at that time. [32]PPIs inhibiting active parietal cell acid secretion are the drugs of choice for PU, H pylori infections, and for the prevention of NSAID-associated ulcers. [33]ith consistent patient tolerability, promising safety profile, and superior antacid capacity, PPIs are gradually becoming the mainstay of therapy for acid-related diseases. [34]Clinical studies have shown that the 4-week cure rate of duodenal ulcers treated with the novel PPI anaprazole is 90.9%. [35]However, the increasing prevalence of antibiotic-resistant strains has become increasingly ineffective.Therefore, tetracycline, which is more effective in eradication, is considered a first-line treatment. [36]ismuth quadruple therapy, which consists of PPIs, bismuth, tetracycline, and nitroimidazole, has been shown to significantly increase the eradication rates of clarithromycin, metronidazole, and dual-resistant strains by 40%, 26%, and 59%. [37]The American College of Gastroenterology, Toronto Consensus recommends bismuth tetracycline for 10 to 14 days as a first-line treatment option because of its high eradication rate, low susceptibility to resistance, and high safety profile. [32,38]oncomitant therapy was PPIs, amoxicillin, clarithromycin, and nitroimidazole therapy for 10 to 14 days.Sequential therapy was PPIs and amoxicillin treatment for the first 5 or 7 days and PPIs, clarithromycin, and nitroimidazole treatment for the next 5 or 7 days.Hybrid therapy is a mixture of sequential and concomitant therapy, with sequential therapy for the first 5 or 7 days and concomitant therapy for the next 5 or 7 days, i.e., PPIs and amoxicillin for the first 5 or 7 days and PPIs, amoxicillin, clarithromycin, and nitroimidazole for the next 5 or 7 days.All 3 have good efficacy against H pylori. [32,38,39] Table 7 Top 10 cited references related to PU.

Rank
Cited references Authors Year Citations 1 Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration.

Conclusion
This study is the first to systematically analyze the literature related to PU using bibliometric methods to provide insights for further research.In the past 15 years, global research on PU has remained hot.We should pay more attention to the papers published in professional journals.We should strengthen the cooperation among countries, institutions, and authors to study PU more deeply, and the research on the diagnosis and pathogenesis of PU is still the future research direction.

Figure 1 .
Figure 1.Detailed process for literature screening.

Figure 3 .
Figure 3. Top 30 countries with research contributions to peptic ulcer.(A) Country collaboration map.(B) Countries' density map.(C) World map of countries' cooperation density.(D) A circle diagram evaluating the international collaboration between clusters.

Figure 4 .
Figure 4. Top 100 institutions with research contributions to peptic ulcer.

Figure 5 .
Figure 5. (A) Top 100 authors with research contributions to peptic ulcer.(B) Top 100 cited authors with research contributions to peptic ulcer.
N. 535 PU = peptic ulcer.published in the United States and focuses on articles in the field of gastroenterology.It is a leading journal in the field of gastrointestinal disease.Marshall B. J. et al published the most cited article, "Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration."This study found that gastritis and PU may be caused by H pylori infection,[14] which was confirmed in subsequent studies for which they were awarded the Nobel Prize in Physiology or Medicine in 2005.It is worth noting that 7 of the 10 most cited papers were on H pylori, which suggests that H pylori has a significant role in PU.The article with the highest intensity of blasts was published by Malfertheiner P et al "Management of Helicobacter pylori infectionthe Maastricht IV/Florence Consensus Report."It discusses the management of H pylori infection and is the most recent of the IF = impact factor, JCR = journal citation reports, PU = peptic ulcer.

Figure 6 .
Figure 6.(A) Top 100 journals with research contributions to peptic ulcer.(B) Top 100 cited journals with research contributions to peptic ulcer.

Figure 7 .
Figure 7. (A) Top 100 cited references with research contributions to peptic ulcer.(B) Top 25 cited references with the strongest citation bursts.

Table 1
Top 10 countries related to PU.

Table 2
Top 10 institutions related to PU.

Table 3
Top 10 authors related to PU.
PU = peptic ulcer.www.md-journal.commuch attention to PU research in recent years.The United States has the second most papers published, only 17 papers less than the number of papers published in China.However, the average citation in the United States is very high.Although only Baylor Coll Med and Michael E DeBakey VA Med Ctr institutions in the top ten rankings belong to the United States, they are the 2 institutions with the highest average citation, which indicates that the quality of the papers in the United States is very high.

Table 4
Top 10 cited authors related to PU.

Table 5
Top 10 journals related to PU.

Table 8
Top 10 keywords related to PU.

Table 6
Top 10 cited journals related to PU. = impact factor, JCR = journal citation reports, PU = peptic ulcer.www.md-journal.com IF